An important approach to developing new drugs is high-throughput screening of compounds. Once a biological molecule is identified as a candidate target for therapeutic intervention thousand of compounds are developed and screened for their ability to interact (e.g. inhibit activity) with the biomolecules.
Many pharmaceutical companies have set minimum goals of screening 500,000 compounds per year against each of more than 100 targets. To reach this goal about 200,000 compounds must be screened every weekday of the year.
There are several screening processes that are utilized for candidate therapeutic agents, including measurement of the binding characteristics between the drug and the identified biomolecules and determination of the effects of the drug agent on biomolecule function. One of the most important screening processes is the use of in vitro cell lines as a bioassay system. This approach allows investigators to determine the effect of the therapeutic agent on the target biomolecule as it exists in a complex, living cellular milieu. The effect of the agent on biomolecule function can be determined, as well as other important parameters such as effective dose range of the agent, half-life of the drug, and ability of the agent to enter a living cell. Moreover, the efficacy and potential toxicity of the drug can be determined by monitoring changes in cellular viability, behavior and phenotype.
Candidate therapeutic agents are often screened in multi-well plates, such as 96- or 384-well plates. Various instrumentation including pipettes and robotic machinery have been designed to accommodate these formats. Multi-well test plates are well known in the art and are exemplified by those described in U.S. Pat. Nos. 4,304,865; 5,219,528; and 5,679,310.
With present techniques only one target may be identified in each well of a multi-well plate. However, many new targeted therapies and drug combinations have the effect of interacting with multiple proteins, for example, with proteins in signaling pathways. It would therefore be desirable to have a method and device for simultaneously surveying the effects of multiple drugs and/or candidate compounds on multiple targets in parallel. Furthermore, it would be desirable for such a method and device to be compatible with the instruments and procedures typically employed in high-throughput screening operations. It would also be desirable for such method and device to be employed for selecting drugs or drug combinations for particular patients based on the effects of the drugs on cellular material from the patient.